Effects of exogenous electromagnetic fields on a simplified ion channel model.

In this paper, we calculate the effect of an exogenous perturbation (an electromagnetic field [EMF] oscillating in the range of microwave frequencies in the range of 1 GHz) on the flux of two ion species through a cylindrical ion channel, implementing a continuous model, the Poisson-Smoluchowski system of equations, to study the dynamics of charged particle density inside the channel. The method was validated through comparison with Brownian dynamics simulations, supposed to be more accurate but computationally more demanding, obtaining a very good agreement. No EMF effects were observed for low field intensities below the level for thermal effects, as the highly viscous regime and the simplicity of the channel do not exhibit resonance phenomena. For high intensities of the external field (>10(5) V/m), we observed slightly different behavior of ion concentration oscillations and ion currents as a function of EMF orientation with respect to the channel axis.

Induced metastable memory in heat shock response.

We studied the dynamics of the Heat Shock Response (HSR) mechanism, and the persistence of a injury-protected state in the cell following the shocks, known as thermotolerance. A series of double shock experiments were performed on Chinese Hamster Ovary (CHO) cells, tracking the dynamics of some components of HSR pathway (the Hsp70 protein level and Hsp70 mRNA transcription rate). The main features of HSR dynamics were well reproduced by a simplified model of the chemical reaction pathways governing the HSR. In particular, the thermotolerance phenomenon could be well characterized by introducing a shock-dependent switch in mRNA halflife, that can be interpreted as a sort of primitive memory at the mRNA level.

Shock wave therapy as an innovative technology in skeletal disorders: study on transmembrane current in stimulated osteoblast-like cells.

Extracorporeal shock wave treatment (ESWT) is successfully used in various musculoskeletal disorders and pathologies. Despite the increasing use of this kind of therapy, some aspects of its mechanism of action are still unclear. In vitro bone cell behavior under ESWT were previously investigated by the present author and MG63 osteoblast-like cells showed an enhancement in proliferation and in the osteoblast differentiation after therapy with a low-energy flux density. The aim of the present study was to evaluate the effect of ESWT on the permeabilization of cell membrane. We characterized physiological changes in the MG63 associated with ESWT generated by an ESW device and patch clamp recording was performed to study ion channels. Experiments were carried out using the whole-cell recording configuration of the patch-clamp technique and the ionic current measurements were performed on cell samples of ESW treated and control groups. The patch-clamp technique showed the effect of ESWT on the amplitude of transmembrane currents. The treatment with ESW enhanced the transmembrane current as well the voltage dependence of Ca-activated and K channels that mediate these currents: the differences between treated cells and control at 80mV were over 1000 pA (p<0.05). These modifications of ion channels activity positively influence cell proliferation (MTT test, p<0.0001) without interfering with the normal synthesis activity of stimulated osteoblasts.

Targeting c-Myc-activated genes with a correlation method: detection of global changes in large gene expression network dynamics.

This work studies the dynamics of a gene expression time series network. The network, which is obtained from the correlation of gene expressions, exhibits global dynamic properties that emerge after a cell state perturbation. The main features of this network appear to be more robust when compared with those obtained with a network obtained from a linear Markov model. In particular, the network properties strongly depend on the exact time sequence relationships between genes and are destroyed by random temporal data shuffling. We discuss in detail the problem of finding targets of the c-myc protooncogene, which encodes a transcriptional regulator whose inappropriate expression has been correlated with a wide array of malignancies. The data used for network construction are a time series of gene expression, collected by microarray analysis of a rat fibroblast cell line expressing a conditional Myc-estrogen receptor oncoprotein. We show that the correlation-based model can establish a clear relationship between network structure and the cascade of c-myc-activated genes.

Quantifying the relevance of different mediators in the human immune cell network.

MOTIVATION: Immune cells coordinate their efforts for the correct and efficient functioning of the immune system (IS). Each cell type plays a distinct role and communicates with other cell types through mediators such as cytokines, chemokines and hormones, among others, that are crucial for the functioning of the IS and its fine tuning. Nevertheless, a quantitative analysis of the topological properties of an immunological network involving this complex interchange of mediators among immune cells is still lacking. RESULTS: Here we present a method for quantifying the relevance of different mediators in the immune network, which exploits a definition of centrality based on the concept of efficient communication. The analysis, applied to the human IS, indicates that its mediators differ significantly in their network relevance. We found that cytokines involved in innate immunity and inflammation and some hormones rank highest in the network, revealing that the most prominent mediators of the IS are molecules involved in these ancestral types of defence mechanisms which are highly integrated with the adaptive immune response, and at the interplay among the nervous, the endocrine and the immune systems. CONTACT: claudio.franceschi@unibo.it.

The effect of noise on a class of energy-based learning rules.

Westudy the selectivity properties of neurons based on BCM and kurtosis energy functions in a general case of noisy high-dimensional input space. The proposed approach, which is used for characterization of the stable states, can be generalized to a whole class of energy functions. We characterize the critical noise levels beyond which the selectivity is destroyed. We also perform a quantitative analysis of such transitions, which shows interesting dependency on data set size. We observe that the robustness to noise of the BCM neuron (Bienenstock, Cooper, & Munro, 1982; Intrator & Cooper, 1992) increases as a function of dimensionality. We explicitly compute the separability limit of BCM and kurtosis learning rules in the case of a bimodal input distribution. Numerical simulations show a stronger robustness of the BCM rule for practical data set size when compared with kurtosis.

Four-part displaced proximal humeral fractures: treatment with hemiarthroplasty.

Between 1996 and 2000 a total of 25 hemiarthroplasties of the shoulder in just as many patients were carried out. A total of 15 were followed-up (minimum 1 year, maximum 5 years, mean 2.5 years; mean age 75.5 years). The Constant score showed a mean of 73.26 points (with a maximum score of 90 and a minimum of 40). One patient obtained a reduced Constant score (40 points) because of severe lesions of the rotator cuff and continuous pain, even during the night. Patients reported that they were satisfied in 75% of cases. We believe that the integrity of the cuff is an essential condition for final success, alongside important indications such as type of fracture, bone quality, age and motivations of the patient, with respect for rules governing method of implantation and protocols for rehabilitation used.

A biophysical model of bidirectional synaptic plasticity: dependence on AMPA and NMDA receptors.

In many regions of the brain, including the mammalian cortex, the magnitude and direction of activity-dependent changes in synaptic strength depend on the frequency of presynaptic stimulation (synaptic plasticity), as well as the history of activity at those synapses (metaplasticity). We present a model of a molecular mechanism of bidirectional synaptic plasticity based on the observation that long-term synaptic potentiation (LTP) and long-term synaptic depression (LTD) correlate with the phosphorylation/dephosphorylation of sites on the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit protein GluR1. The primary assumption of the model, for which there is wide experimental support, is that postsynaptic calcium concentration and consequent activation of calcium-dependent protein kinases and phosphatases are the triggers for the induction of LTP/LTD. As calcium influx through the n-methyl-d-aspartate (NMDA) receptor plays a fundamental role in the induction of LTP/LTD, changes in the properties of NMDA receptor-mediated calcium influx will dramatically affect activity-dependent synaptic plasticity (metaplasticity). We demonstrate that experimentally observed metaplasticity can be accounted for by activity-dependent regulation of NMDA receptor subunit composition and function. Our model produces a frequency-dependent LTP/LTD curve with a sliding synaptic modification threshold similar to what has been proposed theoretically by Bienenstock, Cooper, and Munro and observed experimentally.

Solutions of the BCM learning rule in a network of lateral interacting nonlinear neurons.

We introduce a new method for obtaining the fixed points for neurons that follow the BCM learning rule. The new formalism, which is based on the objective function formulation, permits analysis of a laterally connected network of nonlinear neurons and allows explicit calculation of the fixed points under various network conditions. We show that the stable fixed points, in terms of the postsynaptic activity, are not altered by the lateral connectivity or nonlinearity. We show that the lateral connectivity alters the probability of attaining different states in a network of interacting neurons. We further show the exact alteration in presynaptic weights as a result of the neuronal nonlinearity.

[Proposal of a method of automatic interpretation of images in x-ray computed tomography]. / Proposition de méthode d'interprétation automatique d'images obtenues en tomodensitométrie.

A preliminary study is described relative to the possibility of using methods of automatic image interpretation in the field of biomedical images. These general methods are capable of recognizing characteristic shapes inside the image. In this paper, the structures are described and interpreted. These methods are capable of outlining shapes which are important from a clinical point of view--e.g., spine, vertebrae. They can also evaluate the shapes by plausible methods, to explain the meaning of the whole image. A feasibility study is described concerning the automatic recognition of vertebral contour in axial CT images. The results suggest that the employed techniques can be used in real diagnostic applications.

[A proposed method for the automatic interpretation of images obtained by computer tomography]. / Proposta di un metodo di interpretazione automatica di immagini ottenute con tomografia computerizzata.

A preliminary study is described relative to the possibility of using methods of automatic image interpretation in the field of biomedical images. These general methods are capable of recognizing characteristic shapes inside the image. In this paper the structures are described and interpreted. These methods are capable of outlining shapes which are important from a clinical point of view--e.g., spine, vertebrae. They can also evaluate the shapes by plausible methods, to explain the meaning of the whole image. A feasibility study is described concerning the automatic recognition of vertebral contour in axial CT images. The results suggest that the employed techniques can be used in real diagnostic applications.

[Role of computerized tomography in the diagnosis and evaluation of aneurysms of the abdominal aorta]. / Ruolo della tomografia computerizzata nella diagnosi e nella valutazione degli aneurismi dell'aorta addominale.

The authors report their experience in CT diagnosis of abdominal aorta aneurysms and surgical complication in synthetic aortic grafts. This work is based on a study of 47 patients. Findings, methods, indications and limits of CT in the pathology of aortic aneurysms are shown and discussed.